Analysis of the mechanism of neonatal tolerance induction to the alloantigenic determinants of the H-2 complex will proceed in the direction of in vitro identification of the presence of precursor cells capable of differentiating into effector T cells. Evidence will also be sought for the presence of suppressor T cells in animals rendered neonatally tolerant using adoptive transfer studies in vivo and employing appropriate in vitro correlates. Biochemical and functional characterization of the putative products of the hamster major histocompatibility complex will be extended using xenoantisera directed at hamster lymphoid cells, and by attempting to identify the specific cell responsible for cell mediated killing of virus infected hamster target cells. The contribution of Langerhans cells in the skin to the induction of specific sensitization as well as specific unresponsiveness to contact allergens will be analyzed using recombinant strains of mice differing at various portions of the H-2 complex, as a means of localizing antigen presentation to those cells bearing uniquely the determinants uncoded for by the I region of murine H-2. Using various strain combinations of inbred mice and rats, differing at the major histocompatibility locus, appropriate matings will be set up to produce segregating populations of R2 backcross progeny. The influence of specific sensitization of the mothers on the expected MHC phenotype ratios will be studied using appropriate typing sera.